Onapristone (ONA) ((8S,11R,13R,14S,17S)-11-[4-(dimethylamino)phenyl]-17-hydroxy-17-(3-hydroxypropyl)-13-methyl-1,2,6,7,8,11,12,14,15,16-decahydrocyclopenta[a]phenanthren-3-one) is an anti-progestin drug and progesterone receptor antagonist has the following structure:

Onapristone is known to be an amorphous compound. For example, Onapristone has previously been isolated as an amorphous solid and as a yellow oil. Neef, et al. Steroids, 1984, 44, 349; Neef, et al., DE3321826. In contrast to onapristone, (3-Acyloxypropyl)-derivatives of onapristone were identified as crystalline. See U.S. Pat. No. 4,780,461. Recently, however, crystalline forms of onapristone have been identified. See, e.g., U.S. Patent Publication Number 2014/0271819.
The term “amorphous,” as used herein, refers to the non-crystalline form of a chemical compound. Whereas the crystalline forms of a compound are characterized by structures assembled by the repetitive building up of fundamental units containing the molecules of the compound (known as unit cells), amorphous compounds have no such long-range repetitive structure, and are characterized by short-range, random ordering. Consequently, the lack of crystalline structure inherent to an amorphous compound may lead to significant differences in the physical and chemical properties of the compound, such as its solubility, dissolution rate, stability, bioavailability, and efficacy.
The amorphous form of a drug substance can be compared to crystalline forms of the compound using by a variety of techniques including, but not limited, to melting point, thermogravimetric analysis (TGA), differential scanning calorimetry (DSC), X-ray powder diffraction (XRPD), high performance liquid chromatography (HPLC), Raman microscopy, FT-IR spectroscopy, and solid-state nuclear magnetic resonance (ssNMR). The physical stability of the amorphous form of a compound can be measured, for example, under conditions where the temperature and humidity in the environment are controlled for various time periods.
The term “co-precipitate” refers to the simultaneous precipitation of more than one compound together in a single-phase solid form from a solution. The term “precipitate” refers to the formation of a solid from a liquid solution. Precipitates can be used, for example, to modulate the properties of a chemical compound (e.g., bioavailability, pharmacokinetics, stability).